It was found, against our expectations, that the cationic copolymers of U.S. Pat. No. 4,816,540 are very effective as a non-viral gene delivery vector.
Recently, in vivo gene delivery has allowed the study of gene expression and function in animal models via insertion of foreign genes or alteration of existing genes and/or their expression patterns. The transfection mechanism between transferred DNA or RNA and a cell has been clearly studied and clinical tests for transfection have become easy to carry out using a viral vector. However, some dangerous adverse effects remain associated with the use of viral vectors. Non-viral gene delivery vectors may be a key technology in circumventing the immunogenicity inherent in viral-mediated gene transfer.
It is expected that non-viral vectors, such as the DEAE-dextran copolymer of this invention (Example 1), will increase safety by minimizing the incidence of serious diseases resulting from the immunogenicity inherent in viral vectors.
The invention of U.S. Pat. No. 4,816,540 provides a novel graft-copolymer that is composed of a cationic derivative of a water-soluble linear polymer and an olefin monomer. The invention described in U.S. Pat. No. 4,816,540 also provides a method of graft-polymerizing an olefin monomer onto a cationic derivative of a water-soluble linear polymer in water using ceric ammonium nitrate to obtain a stable and soap-less latex of the graft-copolymer. Namely, the obtained latex sensitized with an antibody or an antigen is agglutinated using an antigen or an antibody, and it can be confirmed rapidly whether the antigen or the antibody is present. The latex used for the L.A. (Latex Agglutination) test is typically a pure, stable and soapless substance and is also very effective as a non-viral gene delivery vector.
It is shown in U.S. Pat. No. 3,989,656 that a dextran-alkyl methacrylate graft composition is obtained by polymerizing an olefin monomer onto a water-soluble linear polymer, such as dextran, in water using ceric ammonium nitrate.
The present invention provides a novel graft-copolymer for a non-viral gene delivery vector that is composed of a cationic derivative of a water-soluble linear polymer and an olefin monomer.
The present invention also provides a method of graft-polymerizing an olefin monomer onto a cationic derivative of a water-soluble linear polymer in water using ceric ammonium nitrate to obtain a stable and soapless latex of the graft-copolymer, which is very effective as a non-viral gene delivery vector.